Tautomeric trans-(.+-.)-5-substituted-7-permissibly-substituted-4,4a,5,6,7,8,8a,9-oct ahydro-1H(and 2H)-pyrazolo[3,4-g]quinolines (I and II), active prolactin inhibitors and useful in the treatment of Parkinsonism, are described in Kornfeld and Bach, U.S. Pat. Nos. 4,198,415, 4,230,861 and 4,367,231. ##STR1## in which R is C.sub.1-3 alkyl or allyl.
The hypotensive activity of one of the trans-(-)-stereoisomers, 4aR,8aR-5-n-propyl-4,4a,5,6,7,8,8a,9-octahydro-1H(and 2H)-pyrazolo[3,4-g]quinoline (the tautomeric pair III and IV where R is n-propyl) is disclosed by Hahn et al., J. Pharm. Exper. Therap., 206 (1983). Methods for preparing C-3 alkylated octahydro-1H(and 2H)-pyrazolo[3,4-g]quinolines have not been previously known.
The octahydropyrazoloquinolines of the above Kornfeld-Bach patents are prepared according to Reaction Scheme 1. ##STR2##
In this Scheme, a trans-(.+-.)-1-alkyl- or allyl-6-oxodecahydroquinoline (V) is condensed with dimethylformamide dimethylacetal to yield (VI) which, on reaction with hydrazine, yields the tautomeric pair (I) and (II).
The copending application of Schaus, Ser. No. 384,817, filed June 3, 1982, abandoned, provides an alternate method of preparing (V) and the copending application of Schaus and Booher, Ser. No. 439,107, filed Nov. 3, 1982, U.S. Pat. No. 4,471,121 issued 9/11/84 provides a method of resolving (V) to yield the trans-(-)-(4aR,8aR)stereoisomer (Va), or trans-(+)stereoisomer, condensation of which with dimethylformamide dimethylacetal yields (VIa) which, on reaction with hydrazine, yields the tautomeric pair (III) and (IV), or the corresponding trans-(+) pair.
Another copending application of Schaus, Ser. No. 438,834, filed Nov. 3, 1982, abandoned, provides an alternate intermediate, trans-(.+-.), trans-(+) or trans- (-)-7-formyl-1-alkyl-6-oxodecahydroquinoline which, on reaction with hydrazine, yields the tautomeric pairs (I) and (II) or (III) and (IV), and the trans-(+) pair depending on whether the trans-(.+-.)-racemate, the trans-(+) or the trans-(-)-stereoisomer is used as the starting material.
The bicyclic ketones (V) and (Va) are also used as a starting material to prepare a series of octahydro-2H-pyrrolo[3,4-g]quinolines via the intermediates (VI) and (VIa) which are condensed with a glycinate salt (rather than hydrazine) to yield the desired tricyclic compounds--see U.S. Pat. No. 4,311,844 (inventors Bach and Kornfeld), col. 3, Reaction Scheme 1. Compounds according to I-IV in which R is allyl and the corresponding pyrroloquinolines are prepared from products in which R is CN or benzyl, by removing the CN or benzyl group and then allylating the resulting secondary amine wherein R is H with an allyl halide.
The prior art cited above does not provide octahydropyrazolo[3,4-g]quinolines having an alkyl substituted in the 3-position of the pyrazole ring, and it is an object of this invention to provide such novel compounds. It is also an object of this invention to provide entirely novel tricyclic compounds and to provide methods for their synthesis.